The Course

About Susan Walsh

Assistant Professor of Biology Susan Walsh focuses her research on mitochondrial trafficking in the nervous system during zebrafish development. Surprising to many students, mitochondria are not the static kidney beans typically shown in electron micrographs but rather, are dynamic organelles that form elegant networks in a cell. Their motion is dependent on signaling molecules and microtubule-binding proteins. Using transgenic zebrafish with fluorescent mitochondria allows Walsh to watch these events in a living animal.

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In this experiment, we set up two tanks A and B. In tank A, we put the wild types and heterozygotes, and in tank B, we put the m homozygotes.Let us provide the residents of tank A (the darker ones) with maze training, which offers a learning opportunity to get more food, but not allow fish in tank B to have that training. Let us consciously label maze ability as ‘‘intelligence’’. After 2 weeks of testing, the fish in tank A will be measured as more ‘‘intelligent’’ than those in tank B (see figure below).Therefore, we can conclude that darker color indicates smarter fish.

Student Response

“The interpretation of the zebrafish experiment is flawed because it does not take training effects into account. The darker fish are obviously going to perform better on the maze test because they have performed the activity before and have had positive reinforcement in the form of food provided to reinforce their behavior. The lighter skinned fish may have been performed just as well if they had received the same training. In order to prove that the darker fish were truly more intelligent, a group of control fish would have to be created for both colors. The experiment could be reset so that 1 group of darker and 1 group of lighter fish gets maze training and a group of both doesn’t get the training. By comparing all four groups some minute correlation could be made, but even then a variable such as intelligence can be hard to objectively measure. Truly objective measuring requires testing that is much more comprehensive then a maze.

This experiment becomes much more complicated when used as an analogy to the nature versus nurture debate. Humans are a combination of nature versus nurture; our physical and mental traits are a combination of our environment and our genetics. Academic ability is an excellent example of nature/nurture. Performance in a traditional school setting is certainly affected by genetics. Autism would be an example of nature and nurture. An autistic child may be incapable of reading at an age appropriate level depending on where the child is on the autism spectrum. However, that child may never learn to read or even interact in any manner without academic and cultural stimulus, which is the environment exerting an effect.

The autism example can be compared to the zebrafish experiment. The “dark” fish that didn’t perform well in the maze may not have done well because they didn’t have any practice like the “white” fish did. The only thing the zebrafish experiment proved was that nature and nurture goes hand in hand and that one cannot be analyzed or studied without considering the other.”

Student Response

“In our Human Genetics biology class, we looked at a series of experiments involving fish. One of these involved testing the intelligence of the fish. The fish were split into two groups and then put into separate tanks. One tank was trained using a maze to find food, whereas the other tank was not. When they were put to the test, only the trained group was able to find the food in the maze. The researchers equated this with the fishes’ genetic intelligence.

In class, we were asked whether this was a legitimate way to reason with the results, and if it could apply to humans as well. This reasoning is definitely completely faulty. The trained fish were only able to find the food because the environment in which they had been raised. The same goes for humans. If someone is raised in a low-income area with no access to good schools or other resources, they may not be as successful as a more wealthy and fortunate person. In the past, races were discriminated against when some people tried to say they were less intelligent than others. However, it has been proven time and time again that intelligence is not genetic and has nothing to do with race. Intelligence is a product of environmental factors.”

Student Response

“In our biology course, we used hypothetical fish experiments to study and better understand human ancestry in relation to biological problems. The specific experiment my group was assigned to compromised of two fish tanks A and B. In tank A we placed all of the wild type (darker fish) and heterozygotes (intermediate color), and in tank B we put all the homozygotes (the lighter fish). The fish in tank A were provided with maze training, which allowed them to learn how to obtain more food. The fish in tank B were not provided this same training. The maze ability in the experiment is labeled as “intelligence”, and after two weeks the results of the experiment concluded that the darker color is an indicator of smarter fish.

There are many problems with the findings of this fish experiment. First, we can look at it in terms of the “one-drop” rule in the US, where any individual with African blood, regardless of what they look like, is deemed to be African. The “one-drop rule” can be applied to the fish because both the wild type and the heterozygous fish were placed in the same tank. The experiment is also flawed because only the fish in tank A were provided with maze training. One cannot conclude that the darker fish are more intelligent if the lighter fish aren’t given the same opportunity to prove their intelligence. We can relate this experiment to human beings because environmental factors such as access to education or a nutritional diet play a role in how “intelligent” an individual is perceived to be. Race or skin color has nothing to do with it.”

Student Response

“While the term race could be said to represent geographically isolated breeding populations wherein certain characteristics arise at higher frequencies than in other populations of that species (Collins 2010, 144), the application of race to the biological sciences is often tenuous, with variations of specific traits often used erroneously to determine the frequency of other traits and ancestry. In particular, skin color is often mistakenly used to determine one’s ethnic heritage, as well as other traits (such as intelligence or a propensity to develop an illness) that may be unrelated to skin color. As environmental factors, such as habitat, economics, diet, and education, also impact traits or the valuation of certain traits, it is unfeasible to separate nature from nurture, particularly in regard to race.

Three zebrafish experiments illustrate the problem with ascribing biological issues with race: In one experiment, wild type (+/+) and heterozygotes (m/+) are placed into one tank (tank A), while homozygote “mutants” (m/m) are placed in another tank (tank B). The fish in tank A are fed salty food, thereby causing high blood pressure only in that population. Genome sequencing is conducted to reveal single nucleotide polymorphisms (or SNP’s) associated with the high blood pressure phenotype (or trait). The differing SNP’s are determined to not only contribute to pigmentation, but to high blood pressure (the population of tank A is darker/more pigmented than the population in tank B). In the second experiment, the fish are interbred over multiple generations to produce multiple variations in pigmentation from darkest (+/+) to lightest (m/m) in varying ratios. An SNP (SNP M) is found only in the lightest (m/m) fish, unlinked to the chromosome that contributes to pigmentation, and causes diabetes. As such, treatment for diabetes in only administered to the light fish (m/m); there is nothing stating that only those who are sick are given the medication. In the third experiment, the fish are again separated into two tanks, with the darker fish (wild type and heterozygote) in tank A, and the lighter fish (mutant) in tank B. The population in tank A undergoes maize training for food, while the population in tank B does not. It is determined that the fish in tank A (the darker fish) are “more intelligent” since they have been provided with, and mastered, maize training, which is considered a measure of intelligence.

It is clear that none of these experiments prove a connection between pigmentation and other traits. In the first experiment, only one population (tank A) is given salty food; its environment is therefore different than that of its neighbors (tank B). The decision to single out one pigment and apply different environmental pressures does not prove that the fish in tank A, because they are darker in color, have a higher risk of hypertension. All that has been proven perhaps is that fish fed a saltier diet have an increased risk for developing the disease. Likewise, targeting only the fish with the lightest pigmentation (m/m) in a highly varied population, and administering medication only to those fish who look a certain way presumes that no heterozygote could also have diabetes and need treatment; it also assumes medications are necessary based on a SNP and not the exhibition of disease. Perhaps most disturbing is the third experiment, in which intelligence is attributed to an arbitrary measure—maize training—and attributed to the sole population given the opportunity to maize train. Since the populations were separated on the basis of color, it follows that the color allowed to maize train (or be educated) would be considered more intelligent than the fish of another color.

If we apply these same conditions to a group of people exhibiting certain phenotypes (such as hair and skin color), we begin to see how attaching biological issues—such as disease or intelligence—to race is erroneous and leads to few solutions. In regard to the first and second experiments, we can see how attributing health problems on the basis of race fails to realize environmental factors and the diverse range of genotypes within the human population. Having a propensity to develop certain illnesses does not mean you will; one’s lifestyle and economic status may be regarded as catalysts for disease manifestation as well. In regard to the third experiment, attributing intelligence to race neglects the role economics and culture may have on educational resources. It also fails to realize how inaccurate and biased intelligence testing may be in assessing who is intelligent, and in what way. Just as the zebrafish experiments fail to solve biological issues due to their reliance on non-factors, such as fish color, human experiments often fail in the same way. Even worse, the use of race in solving human quandaries has led to such atrocities as the Tuskegee syphilis experiments, and the use of I.Q. tests to censure certain immigrant groups from entering the United States.”

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For homework, students were asked to analyze a series of zebrafish experiments to determine if the conclusions were scientifically valid.Most students quickly identified flaws in experimental design.During class, they discussed the experiments in groups and then related them to historical conclusions about race in humans, in terms of medicine or intelligence.The assignments are below and were based on suggestions from Cheng K. C. 2008. Skin Color in Fish and Humans:Impacts on Science and Society. Zebrafish 5: 237-242.

Thinking about different genotypic arrangements of fish living in different tanks can clarify the difference between the effects of genotype and environment. Let us start with an ancestrally dark fish that is homozygous wild-type (+/+) and a homozygous mutant (m/m) fish for a pigmentation mutation in which heterozygotes (m/+) are of an intermediate color. A cross between the two original strains yields all m/+ heterozygotes. So what do scientists call these individuals?We define their skin color phenotype as intermediate color, know that they are heterozygotes by genotype, and also know that half of their genomes are from the wild-type background and half from the mutant background.

Race and Medicine

In this experiment, we set up two tanks A and B.In tank A, we put the wild types and heterozygotes, and in tank B, we put the m homozygotes.We feed population A food that is more salty than the food fed to population B, causing high blood pressure (see the figure below). Geneticists then do genome wide sequencing to try to identify SNPs associated with the high blood pressure phenotype.They identify a series of SNPs that are different between tank A and tank B, and these SNPs are also associated with pigmentation.The researchers then conclude that the genes for dark pigmentation are linked to high blood pressure.

In this experiment, we allow many generations of interbreeding. A wide range of proportionality of genomes of each of the original strains will be generated (1/2m; 1/4m; 2/3m; 1/16m; etc). These fish will display a range of pigmentation from very dark (mostly +/+ genome) to very light (mostly m/m genome).Let us say that SNP M is present originally only in the pale m/m population, is unlinked to the chromosome containing pigmentation gene m, and causes diabetes. You discover a drug that will cure the diabetes phenotype associated with SNP M and only treat the lightest colored fish with the drug.

Student Response

“Race is a social construct that attempts to categorize people into specific groups based on cultural, geographical, and/or biological characteristics. That being said, it is not a reliable source to use as the basis of human biological problems. However, there have been numerous instances where medical companies and medical practitioners have tried to use race for just this purpose. One infamous example that arose in recent years involved the development and marketing of a race-specific drug, BiDil, that was intended as a treatment for heart failure in African-Americans. After conducting tests and research on more than 1000 subjects, the black men and women that received the drug in the trials reportedly experienced a 43% drop in deaths over two years. The company that owned the drug, NitroMed, determined this as a success and began to promote BiDil as a drug intended for African-American use. The problem that arose was the drug was labeled with “BiDil is indicated for the treatment of heart failure as an adjunct to standard therapy in self-identified black patients”. As a result, this created the false impression that self-identifying as African-American would make a person different, biologically, in comparison to another group. Therefore, those who identified themselves with the black race, whether they were of African ancestry or not, may or may not have been able to benefit from the drug. Also, though the tests were only completed on a group African-Americans, there was no definitive testing completed that revealed if those who were not African-American would have the same or other benefits from the drug. This situation therefore made NitroMed’s attempt to promote BiDil as a drug exclusively for American-Americans as extremely misleading and reemphasizes the unreliability that comes from trying to use race as the basis of human biological problems. This same situation involving flawed testing and its improper correlation with race was also exemplified in the theoretical fish experiments that we studied in Bio 111. In each of the experiments, there was a variable that was not applied equally to all of the groups of fish that had different pigmentation genes. This then lead to conclusions regarding health conditions that were incorrectly associated with the skin color of the fish, mirroring the same misleading conclusions that NitroMed came to after the testing and promotion of BiDil exclusively for African-Americans.”

Student Response

“Earlier in the semester we were introduced to a fish experiment where the original fish were either light or dark. After breeding between each other there were fish that ranged in color from very light to very dark and colors in between. In this experiment the researchers discovered that there was diabetes in some of the fish but that it originated from the very light fish. Even though the fish had breed amongst each other and were a spectrum of different colored fish, the researchers decided to only give medicine for diabetes to the light fish who “originated the disease”. This experiment brings up memories of BiDil, which was the first medicine specifically targeted for African Americans. BiDil is used in the treatment of those with heart disease and is specifically marketed for African Americans. The problem that arises when you market or sell a medicine to only certain races or types of people is that you completely rule out the hope that it may also help others in a different race or group. People who see the drugs marketed to another race will be discouraged from buying it and even though it could help them they will never get the chance to use it. The result of simply marketing drugs to one race or group of people can negatively affect a lot of people that are hurting and could potentially benefit from it.”

Student Response

“There is an ethical problem and biological problem with this experiment. First and foremost, this experiment is failing to treat the lightest colored fish based on their genotype instead of their phenotype. Also because the SNP M is unlinked to a chromosome, whether the fish is pale or not is not enough information to consider that they have the SNP M for the mutation. The light fish are once again being treated for being pale and not for the presence of the mutation.

This fish experiment can be applied to humans as well and is very similar to the BiDil situation that was offered to African Americans because of their race. The genotype is more important to consider when administrating drugs and medications because this shows the biological make up of someone’s genes. When looking at race, by this point in history it is irrelevant. Many races have over and over again merged, forming a very mixed population of humans. This broad range of people makes it is impossible to treat a person because it is rare that you find an individual that is 100% of any race. Conclusively, genotype prevails over phenotype when treatment, or drugs should be considered for any species.”

Student Response

“In class, we were given a hypothetical experiment involving zebrafish. It started with two types of fishes, dark and light colored, who mated then and their children mated and so on for many generations until there were a ton of fish with varying shades. The thing about these fish was that the initial light colored fish had a mutation in their DNA that caused them to have diabetes. This mutation, although in the light colored fish, was not genetically linked to the DNA for light color. The experimenters have a drug that treats diabetes and to test it out, they treat only the light colored fish.

Looking at this experiment, it’s plain to see that these experiments are botching things up. They were treating only light colored fish for diabetes when there’s no real connection between light color and diabetes. While this seems like an obvious blunder, such a thing happened in real life, except instead of zebrafish and diabetes it was African-American and congenital heart failure. A company created a drug called BiDil that treated heart failure. It was touted as a drug for African-Americans based on a study where they took a lot of African Americans and treated them with the drug. Just like the zebrafish experiment, heart failure was not linked to having darker skin. In fact, BiDil could be used to treat pretty much everyone of any color. It’s just that the study didn’t involve everyone, so experimenters were making wrong assumptions about heart failure and skin color. It was a highly controversial issue and showed a gross neglect on proper and impartial testing. In science and most other things in life, it is important to be unbiased in our beliefs and decisions; they should be based on fact and experience instead of the other way around.”